Hydrogen Sulfide and Hemeproteins: Knowledge and Mysteries

Abstract

Historically, hydrogen sulfide (H₂S) has been regarded as a poisonous gas, with a wide spectrum of toxic effects. However, like ·NO and CO, H₂S is now referred to as a signaling gas involved in numerous physiological processes. The list of reports highlighting the physiological effects of H₂S is rapidly expanding and several drug candidates are now being developed. As with ·NO and CO, not a single H₂S target responsible for all the biological effects has been found till now. Nevertheless, it has been suggested that H₂S can bind to hemeproteins, inducing different responses that can mediate its effects. For instance, the interaction of H₂S with cytochrome c oxidase has been associated with the activation of the ATP-sensitive potassium channels, regulating muscle relaxation. Inhibition of cytochrome c oxidase by H₂S has also been related to inducing a hibernation-like state. Although H₂S might induce these effects by interacting with hemeproteins, the mechanisms underlying these interactions are obscure. Therefore, in this review we discuss the current state of knowledge about the interaction of H₂S with vertebrate and invertebrate hemeproteins and postulate a generalized mechanism. Our goal is to stimulate further research aimed at evaluating plausible mechanisms that explain H₂S reactivity with hemeproteins. Antioxid. Redox Signal. 15, 393–404.